Evidence map›Paper›PMID 40991418›Full record

ArticleMolecular biology of the cell2025

Metabolic programming defines oxygen-sensitive subpopulation hierarchies and patterning in collective invasion.

Veronika Y Matsuk, Tala O Khatib, Landon J Marcus, Isaac E Robinson, Yuan Liu, Janani K Pasupathy, Mala Shanmugam, Janna K Mouw, Adam I Marcus

Abstract read
In one paragraph

Article in Molecular biology of the cell, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Veronika Y MatsukDepartment of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA 30322.
Tala O KhatibDepartment of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA 30322.
Landon J MarcusCommunity Scientist, Atlanta, GA 30033.
Isaac E RobinsonDepartment of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA 30322.
Yuan LiuDepartment of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA 30322.
Janani K PasupathyEmory Integrated Computational Core, Emory University, Atlanta, GA 30322.
Mala ShanmugamDepartment of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA 30322.
Janna K MouwDepartment of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA 30322.
Adam I MarcusDepartment of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA 30322.

Funding

Implementing a Maternal health and PRegnancy Outcomes Vision for Everyone (IMPROVE)UL1TR002378 · NCATS · EMORY UNIVERSITY · PI Andres J Garcia, Elizabeth O. Ofili · 2017 to 2026
$92.1M
Winship Cancer Institute Cancer Center Support GrantP30CA138292 · NCI · EMORY UNIVERSITY · PI Ragini Reiney Kudchadkar · 2009 to 2026
$47.5M
Project 3: Inhibiting FAK to enhance immune checkpoint inhibitor therapy in LKB1-mutant lung adenocarcinomaP01CA257906 · NCI · EMORY UNIVERSITY · PI Yuan Liu · 2022 to 2026
$10.7M
Project 3: Targeting Bax signaling to overcome treatment resistance in NSCLCP50CA217691 · NCI · EMORY UNIVERSITY · PI FU, HAIAN, RAMALINGAM, SURESH S · 2019 to 2024
$10.1M
Spatiotemporal interrogation of metabolic cooperation between heterogenous lung cancer subpopulations in collective cell invasionR01CA247367 · NCI · EMORY UNIVERSITY · PI MARCUS, ADAM I., SHANMUGAM, MALATHY (MALA) · 2021 to 2025
$2.3M
Atypical Angiogenic Mimicry During Collective Lung Cancer InvasionR01CA236369 · NCI · EMORY UNIVERSITY · PI MARCUS, ADAM I. · 2019 to 2023
$1.8M
Deconstructing the collective invasion pack to define Myo10 functionR01CA250422 · NCI · EMORY UNIVERSITY · PI MARCUS, ADAM I. · 2020 to 2024
$1.8M
Deconstructing cellular heterogeneity and subpopulation cooperation in non-small cell lung cancer metastasisR50CA265345 · NCI · EMORY UNIVERSITY · PI MOUW, JANNA K · 2021 to 2025
$720k
NCATS NIH HHS UL1 TR002378NCI NIH HHS P01 CA257906NCI NIH HHS P30 CA138292NCI NIH HHS P50 CA217691NCI NIH HHS R01 CA236369NCI NIH HHS R01 CA247367NCI NIH HHS R01 CA250422NCI NIH HHS R50 CA265345
6 · The paper itself

Abstract

Phenotypic heterogeneity-distinct molecular and behavioral variations within a population-significantly influences collective invasion and tumor progression. Here, we use a molecular approach to explore how the underlying metabolic heterogeneity in non-small cell lung cancer (NSCLC) influences invasion and pack patterning. Assessment of  three-dimensional (3D) pack patterning revealed invasive heterogeneity across NSCLC cell lines and patient-derived samples. Flow cytometry identified IL13RA2 as a biomarker for invasive potential, enabling isolation of subpopulations with distinct invasive characteristics. By integrating a cell surface biomarker (IL13RA2±) with mitochondrial membrane potential (TMRM), we identified and isolated three distinct subpopulations. Two-dimensional (2D) analyses revealed differences in mitochondrial polarity and transcriptional programs associated with migration and oxygensensitivity. In 3D, these subpopulations invaded with distinct patterns, from contiguous circular packs to structured chains. Assessments under varied oxygen tension demonstrated that oxygen availability and subpopulation metabolism together influence collective invasion patterning. When recombined at ratios recapitulating the original population, both stochastic and opportunistic cooperative dynamics emerged, dependent on subpopulation composition and oxygen levels. Our molecular approach, integrating cell surface and metabolic characteristics, enables the isolation of unique subpopulations and demonstrates that phenotypic and metabolic heterogeneity, population composition, and oxygen availability collectively pattern invasion packs and drive collective invasion.

Indexed as

Carcinoma, Non-Small-Cell LungLung NeoplasmsMetabolic ReprogrammingMitochondriaOxygenBiomarkers, TumorCell Line, TumorCell MovementFlow CytometryGene Expression Regulation, NeoplasticHumansInterleukin-13 Receptor alpha2 SubunitMembrane Potential, MitochondrialNeoplasm InvasivenessBiomarkers, TumorIL13RA2 protein, humanInterleukin-13 Receptor alpha2 SubunitOxygen

Identifiers

PMID40991418
PMCPMC12562065

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.